Generally, mint lactone is a natural component of mint oil, and a potential precursor to 3,6-dimethylhexahydrobenzofuran-2-one, a valued flavor and fragrance ingredient. Multiple efforts have been made to cost effectively produce mint lactone, which include the hydrogenation and elimination of hydroxymenthofurolactone (I), which comprises the formula:

as described in Koch (U.S. Pat. No. 6,512,126), and the treatment of 3-methylcyclohexanone (II), which comprises the formula:

Compound (II) is treated with methyl pyruvate in a multi-step synthesis involving sodium borohydride and iron chloride as described in Xiong (CN 102,850,309). While both of these approaches are practicable, they use relatively expensive starting materials and reagents (e.g., Pd/C, NaBH4). Another major drawback to these methods is that these methods do not produce highly enantio-enriched material. Additional approaches, including the use of citronellal (Shishido, et al., Tetrahedron Letters, 33(32), 4589-4592 (1992)), and alkynyl aldehydes (Gao et al., Journal of Organic Chemistry, 74(6), 2592 (2009)), have also been described, but again lack economic feasibility.
Through use of naturally occurring and commercially available isopulegol (III), a key precursor (IV) in the synthesis of mint lactone (V), can be easily obtained that allows the desired natural stereochemistry to be retained all while using inexpensive and commercially available reagents as shown in the following equation, Scheme A:

Although isopulegol (III) has been used as a starting material for the synthesis of enantiopure mint lactone in the past (Chavan et al., Tetrahedron Letters, 49(29), 6429-6436 (1993)), the approaches appear to have the common problem of being too costly to be commercially attractive, including the use of hydroboration and deprotonation with lithium diisopropyl amide under cryogenic conditions.
As a result of the limitations of these previous approaches, mint lactone and several related materials, such as 3,6-dimethylhexahydrobenzofuran-2-one (also known as Koumalactone®) have been very expensive to obtain commercially, especially with the desired stereochemistry, and therefore their use has been limited.
Additionally, specific isomers of mint lactone's saturated analogs can be difficult to obtain using traditional routes (Gaudin, Tetrahedron Letters 56(27), 4769-4776 (2000); Gaudin (U.S. Pat. No. 5,464,824)). In this regard, the invention described herein addresses these problems. Particularly, through certain aspects of this invention, compound (IV) can be deoxygenated to generate the desired isomers directly in a facile, high yielding manner.
In view of the disadvantages inherent in the known types of methods now present in the prior art, the present invention provides an improved method to produce mint lactone, derivatives thereof, and related materials.